CHARACTERIZING SEQUENCE VARIATION IN THE VP1 CAPSID PROTEINS OF FOOT-AND-MOUTH-DISEASE VIRUS (SEROTYPE-0) WITH RESPECT TO VIRION STRUCTURE

The VP1 capsid protein of foot and mouth disease virus (FMDV) is highl y polymorphic and contains several of the major immunogenic sites impo rtant to effective antibody neutralization and subsequent viral cleara nce by the immune system, Whether this high level of polymorphism is o f adaptive value to the virus remains unknown, In this study we examin ed sequence data from a set of 55 isolates in order to establish the n ature of selective pressures acting on this gene, Using the known mole cular structure of VP1, the rates and ratios of different types of non synonymous and synonymous changes were compared between different part s of the protein, All parts of the protein are subject to purifying se lection, but this is greatest amongst those amino acid residues within beta-strands and is significantly reduced at residues exposed on the capsid surface, which include those residues demonstrated by previous mutational analyses to permit the virus to escape from monoclonal anti body binding; The ratios of nonsynonymous substitution resulting in va rious forms of physicochemically radical and conserved amino acid chan ge were shown to be largely equal throughout these different parts of the protein, There was a consistently higher level of nonsynonymous an d charge radical sites in those regions of the gene coding for residue s exposed on the outer surface of the capsid and a marked difference i n the use of amino acids between surface and nonsurface regions of the protein, However, the analysis is consistent with the hypothesis that the observed sequence variation arises where it is least likely to be disruptive to the higher-order structure of the protein and is not ne cessarily due to positive Darwinian selection.